GENEVA’s proposed cross-study GWAS mirror the meta-analytical approach but with additional challenges anticipated. Some traits, including habitual alcohol and caffeine consumption, physical activity and sleeping behavior are difficult to define with many external factors influencing their measurement. Moreover, very little is known regarding the properties of the discovery process in cross-study analyses of GWAS-derived signals, especially for complex traits. Such approaches are susceptible to the same issues as in single studies pursuing agnostic associations, but have additional caveats to attend to; between-study heterogeneity being a particularly important one [Pereira et al., 2009].
